In rat striatal slices glutamate receptor stimulation at a post-synaptic location leads to a Ca2+-dependent activation of NO-synthase, and to nitric oxide formation that serves as a diffusible signal operative in dopamine release from axonal terminals. The glutamate-elicited release was blocked by NO-L-arginine, an irreversible inhibitor of NO-synthase, and hemoglobin, a scavenger of extracellular NO. In primary cultures of embryonic mesencephalic neurons spontaneously released NO from nucleophiles elicited [3H]dopamine release in a dose-dependent manner that was attenuated by the presence of hemoglobin. NO triggered [3H]dopamine release without involvement of increased Ca2+ currents, or membrane action potential, but in the absence of extracellular Ca2+.